title: Chikungunya virus-like particles are more immunogenic in a lethal AG129 mouse model compared to glycoprotein E1 or E2 subunits.
abstract: Chikungunya virus (CHIKV) causes acute illness characterized by fever and long-lasting arthritic symptoms. The need for a safe and effective vaccine against CHIKV infections is on the rise due to on-going vector spread and increasing severity of clinical complications. Here we report the results of a comparative vaccination-challenge experiment in mice using three different vaccine candidates produced in insect cells by recombinant baculoviruses: (i) secreted (s)E1 and (ii) sE2 CHIKV glycoprotein subunits (2 μg/immunization), and (iii) CHIKV virus-like particles (VLPs) (1 μg E2 equivalent/immunization). These experiments show that vaccination with two subsequent administrations of 1 μg of Matrix M adjuvanted CHIKV VLPs completely protected AG129 mice from lethal CHIKV challenge. Vaccination with E1 and E2 subunits provided partial protection, with half of the mice surviving but with significantly lower neutralizing antibody titres as compared to the VLP vaccinated mice. This study provides evidence that even a modest neutralizing antibody response is sufficient to protect mice from CHIKV infections. Neutralization was the prominent correlate of protection. In addition, CHIKV VLPs provide a superior immune response and protection against CHIKV-induced disease in mice as compared to individual CHIKV-sE1 and -sE2 subunits.
authors.affiliation: Laboratory of Virology, Wageningen University, Wageningen, The Netherlands.
authors.forename: Stefan W
authors.initials: SW
authors.lastname: Metz
authors.forename: Byron E
authors.initials: BE
authors.lastname: Martina
authors.forename: Petra
authors.initials: P
authors.lastname: van den Doel
authors.forename: Corinne
authors.initials: C
authors.lastname: Geertsema
authors.forename: Albert D
authors.initials: AD
authors.lastname: Osterhaus
authors.forename: Just M
authors.initials: JM
authors.lastname: Vlak
authors.forename: Gorben P
authors.initials: GP
authors.lastname: Pijlman
mesh_terms: D018354:Alphavirus Infections / Q000276:immunology / Q000517:prevention & control*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D002646:Chikungunya virus / Q000276:immunology*; D004195:Disease Models, Animal; D051379:Mice; D016019:Survival Analysis; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology; D058425:Vaccines, Virus-Like Particle / Q000008:administration & dosage / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D022223:Vaccines, Subunit; D058425:Vaccines, Virus-Like Particle; D014764:Viral Proteins; D014765:Viral Vaccines
keywords: AG129; Chikungunya virus; E1; E2; Subunits; Vaccine; Virus-like particle